tbuckley/cabot-search huggingface dataset:
Obstructive sleep apnoea and 5-year cognitive decline in the elderly
Authors: Nicola Andrea Marchi, Geoffroy Solelhac, Mathieu Berger, José Haba-Rubio, Nadia Gosselin, Peter Vollenweider, Pedro Marques-Vidal, Julius Popp, Armin von Gunten, Martin Preisig, Bogdan Draganski, Raphael Heinzer
Journal: European Respiratory Journal (2023)

Background The relationship between obstructive sleep apnoea (OSA) and cognitive decline remains controversial, especially in the elderly population. We used data from the HypnoLaus study to assess associations between OSA and longitudinal cognitive changes in a sample of community-dwelling elderly individuals. Methods We studied associations between polysomnographic OSA parameters (of breathing/hypoxaemia and sleep fragmentation) and cognitive changes over a 5-year period, after adjustment for potential confounders. The primary outcome was the annual change in cognitive scores. The moderating effects of age, sex and apolipoprotein E4 (ApoE4) status were also examined. Results 358 elderly individuals without dementia were included (mean± sd age 71.0±4.2 years; 42.5% males). A lower mean peripheral oxygen saturation ( S pO 2 ) during sleep was associated with a steeper decline in Mini-Mental State Examination ( B = −0.12, p=0.004), Stroop test condition 1 ( B =0.53, p=0.002) and Free and Cued Selective Reminding Test delayed free recall ( B = −0.05, p=0.008). A longer time spent asleep with S pO 2 &lt;90% was associated with a steeper decline in Stroop test condition 1 ( B =0.47, p=0.006). Moderation analysis showed that apnoea–hypopnoea index and oxygen desaturation index were associated with a steeper decline in global cognitive function, processing speed and executive function only in older participants, men and ApoE4 carriers. Conclusions Our results provide evidence of the contribution of OSA and nocturnal hypoxaemia to cognitive decline in the elderly population.
ERJ advances: state of the art in definitions and diagnosis of COPD
Authors: Sachin Ananth, John R. Hurst
Journal: European Respiratory Journal (2023)

With high prevalence and high burden, the condition we call chronic obstructive pulmonary disease (COPD) is not so much a respiratory concern as a public-health epidemic [1]. This is particularly true in low- and middle-income countries (LMICs) where most cases remain undiagnosed and untreated. With recent changes to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) definition of COPD [2], and publication of the Lancet Commission on COPD [1], we review the current state of the art in relation to COPD definition and diagnosis, and why remaining inconsistencies matter. Current definitions of COPD are not consistent with diagnostic criteria, contributing to confusion in clinical practice and research https://bit.ly/3IkrZqD
PPAR-γ activation promotes xenogenic bioroot regeneration by attenuating the xenograft induced-oxidative stress
Authors: Tingting Lan, Fei Bi, Yuchan Xu, Xiaoli Yin, Jie Chen, Xue Han, Weihua Guo
Journal: International Journal of Oral Science (2023)

Abstract Xenogenic organ transplantation has been considered the most promising strategy in providing possible substitutes with the physiological function of the failing organs as well as solving the problem of insufficient donor sources. However, the xenograft, suffered from immune rejection and ischemia-reperfusion injury (IRI), causes massive reactive oxygen species (ROS) expression and the subsequent cell apoptosis, leading to the xenograft failure. Our previous study found a positive role of PPAR-γ in anti-inflammation through its immunomodulation effects, which inspires us to apply PPAR-γ agonist rosiglitazone (RSG) to address survival issue of xenograft with the potential to eliminate the excessive ROS. In this study, xenogenic bioroot was constructed by wrapping the dental follicle cells (DFC) with porcine extracellular matrix (pECM). The hydrogen peroxide (H 2 O 2 )-induced DFC was pretreated with RSG to observe its protection on the damaged biological function. Immunoflourescence staining and transmission electron microscope were used to detect the intracellular ROS level. SD rat orthotopic transplantation model and superoxide dismutase 1 (SOD1) knockout mice subcutaneous transplantation model were applied to explore the regenerative outcome of the xenograft. It showed that RSG pretreatment significantly reduced the adverse effects of H 2 O 2 on DFC with decreased intracellular ROS expression and alleviated mitochondrial damage. In vivo results confirmed RSG administration substantially enhanced the host’s antioxidant capacity with reduced osteoclasts formation and increased periodontal ligament-like tissue regeneration efficiency, maximumly maintaining the xenograft function. We considered that RSG preconditioning could preserve the biological properties of the transplanted stem cells under oxidative stress (OS) microenvironment and promote organ regeneration by attenuating the inflammatory reaction and OS injury.
RGS12 represses oral squamous cell carcinoma by driving M1 polarization of tumor-associated macrophages via controlling ciliary MYCBP2/KIF2A signaling
Authors: Gongsheng Yuan, Shuting Yang, Shuying Yang
Journal: International Journal of Oral Science (2023)

Abstract Tumor-associated macrophages (TAMs) play crucial roles in tumor progression and immune responses. However, mechanisms of driving TAMs to antitumor function remain unknown. Here, transcriptome profiling analysis of human oral cancer tissues indicated that regulator of G protein signaling 12 (RGS12) regulates pathologic processes and immune-related pathways. Mice with RGS12 knockout in macrophages displayed decreased M1 TAMs in oral cancer tissues, and extensive proliferation and invasion of oral cancer cells. RGS12 increased the M1 macrophages with features of increased ciliated cell number and cilia length. Mechanistically, RGS12 associates with and activates MYC binding protein 2 (MYCBP2) to degrade the cilia protein kinesin family member 2A (KIF2A) in TAMs. Our results demonstrate that RGS12 is an essential oral cancer biomarker and regulator for immunosuppressive TAMs activation.
NK cells are never alone: crosstalk and communication in tumour microenvironments
Authors: Yongqiang Zhou, Lu Cheng, Lu Liu, Xun Li
Journal: Molecular Cancer (2023)

Abstract Immune escape is a hallmark of cancer. The dynamic and heterogeneous tumour microenvironment (TME) causes insufficient infiltration and poor efficacy of natural killer (NK) cell-based immunotherapy, which becomes a key factor triggering tumour progression. Understanding the crosstalk between NK cells and the TME provides new insights for optimising NK cell-based immunotherapy. Here, we present new advances in direct or indirect crosstalk between NK cells and 9 specialised TMEs, including immune, metabolic, innervated niche, mechanical, and microbial microenvironments, summarise TME-mediated mechanisms of NK cell function inhibition, and highlight potential targeted therapies for NK-TME crosstalk. Importantly, we discuss novel strategies to overcome the inhibitory TME and provide an attractive outlook for the future.
Recent advances and applications of CRISPR-Cas9 in cancer immunotherapy
Authors: Zaoqu Liu, Meixin Shi, Yuqing Ren, Hui Xu, Siyuan Weng, Wenjing Ning, Xiaoyong Ge, Long Liu, Chunguang Guo, Mengjie Duo, Lifeng Li, Jing Li, Xinwei Han
Journal: Molecular Cancer (2023)

Abstract The incidence and mortality of cancer are the major health issue worldwide. Apart from the treatments developed to date, the unsatisfactory therapeutic effects of cancers have not been addressed by broadening the toolbox. The advent of immunotherapy has ushered in a new era in the treatments of solid tumors, but remains limited and requires breaking adverse effects. Meanwhile, the development of advanced technologies can be further boosted by gene analysis and manipulation at the molecular level. The advent of cutting-edge genome editing technology, especially clustered regularly interspaced short palindromic repeats (CRISPR-Cas9), has demonstrated its potential to break the limits of immunotherapy in cancers. In this review, the mechanism of CRISPR-Cas9-mediated genome editing and a powerful CRISPR toolbox are introduced. Furthermore, we focus on reviewing the impact of CRISPR-induced double-strand breaks (DSBs) on cancer immunotherapy (knockout or knockin). Finally, we discuss the CRISPR-Cas9-based genome-wide screening for target identification, emphasis the potential of spatial CRISPR genomics, and present the comprehensive application and challenges in basic research, translational medicine and clinics of CRISPR-Cas9.
The gut microbiome in ARDS: from the “whether” and “what” to the “how”
Authors: Kale S. Bongers, Kathleen A. Stringer, Robert P. Dickson
Journal: European Respiratory Journal (2023)

Recent studies, both clinical and experimental, have established beyond question that the gut microbiome plays an important role in organ dysfunction in critical illness. A recent study in this journal [1] demonstrated that among mechanically ventilated patients, depletion of gut anaerobes ( via anti-anaerobic antibiotics) is associated with a 7% increase in in-hospital mortality. An impressive study in ERJ reveals the importance, and complexity, of the gut microbiome's role in ALI/ARDS <https://bit.ly/3IPCfrt>
The puzzles of lung function interpretation
Authors: Riccardo Pellegrino, Vito Brusasco
Journal: European Respiratory Journal (2023)

The publication of the recent European Respiratory Society/American Thoracic Society technical document on lung function interpretation [1] marks a fundamental step in respiratory medicine that consolidates the scientific work initiated in 1983 and regularly updated over the following years up to the present. It is time to open a frank discussion about important discrepancies between lung function and clinical documents on respiratory diseases <https://bit.ly/3VJeMLY>
Reply: The puzzles of lung function interpretation
Authors: Sanja Stanojevic, David A. Kaminsky, Martin Miller, Bruce Thompson
Journal: European Respiratory Journal (2023)

<b>There is an important discussion to be had regarding the discrepancy between pulmonary function test interpretation standards and clinical guidelines, and the impact this has on the diagnosis and management of respiratory disease worldwide</b>https://bit.ly/3QpFaJ7
Preventing bronchiolitis among infants with non-pharmaceutical interventions outside pandemics: is it realistic?
Authors: Eva S.L. Pedersen, Claudia E. Kuehni
Journal: European Respiratory Journal (2023)

<b>Non-pharmaceutical interventions, such as wearing facemasks and teleworking, may help prevent bronchiolitis among infants; however, we need more knowledge about the feasibility and impact of such interventions outside the COVID-19 pandemic context</b>https://bit.ly/3VOgBHd
Bacterial and Human Cell Mutagenicity Study of Some C 18 H 10 Cyclopenta-Fused Polycyclic Aromatic Hydrocarbons Associated with Fossil Fuels Combustion
Authors: Arthur L. Lafleur, John P. Longwell, Joseph A. Marr, Peter A. Monchamp, Elaine F. Plummer, William G. Thilly, Patrick P. Y. Mulder, Ben B. Boere, Jan Cornelisse, Johan Lugtenburg
Journal: Environmental Health Perspectives (1993)

W0~Cyclopenta-fused polycyclic aromatic
Pre-eclampsia
Authors: Evdokia Dimitriadis, Daniel L. Rolnik, Wei Zhou, Guadalupe Estrada-Gutierrez, Kaori Koga, Rossana P. V. Francisco, Clare Whitehead, Jon Hyett, Fabricio da Silva Costa, Kypros Nicolaides, Ellen Menkhorst
Journal: Nature Reviews Disease Primers (2023)
Selected Articles from This Issue
Journal: Clinical Cancer Research (2023)

Neoadjuvant immune checkpoint blockade increasingly is incorporated into the perioperative treatment setting for solid tumor malignancies, including resectable non-small cell lung cancer (NSCLC).However, long-term outcomes, specifically survival, after treatment with these agents are still maturing.In this article, Rosner and colleagues present the five-year clinical outcomes after neoadjuvant nivolumab for resectable NSCLC, representing the longest follow up data available after neoadjuvant anti-PD-1 therapy in any cancer type.In addition to the durable clinical benefit of neoadjuvant nivolumab highlighted in this report, the examination of key subgroups and biomarkers may help clinicians and investigators as they look to navigate this rapidly evolving treatment landscape.Several questions remain on how to further optimize perioperative outcomes for patients with resectable NSCLC, making long-term follow up data, as reported here, particularly valuable.
CMV serostatus and T-cell repertoire diversity 5 years after allogeneic hematopoietic stem cell transplantation
Authors: Zuleika Calderin Sollet, Antonia Schäfer, Sylvie Ferrari-Lacraz, Stavroula Masouridi-Levrat, Anne-Claire Mamez, Amandine Pradier, Federico Simonetta, Yves Chalandon, Jean Villard, Stéphane Buhler
Journal: Leukemia (2023)
Transfer RNA-derived small RNAs in tumor microenvironment
Authors: Mei Yang, Yongzhen Mo, Daixi Ren, Shun Liu, Zhaoyang Zeng, Wei Xiong
Journal: Molecular Cancer (2023)

Transfer RNAs (tRNAs) are a class of non-coding RNAs responsible for amino acid translocation during protein synthesis and are ubiquitously found in organisms. With certain modifications and under specific conditions, tRNAs can be sheared and fragmented into small non-coding RNAs, also known as tRNA-derived small RNAs (tDRs). With the development of high-throughput sequencing technologies and bioinformatic strategies, more and more tDRs have been identified and their functions in organisms have been characterized. tRNA and it derived tDRs, have been shown to be essential not only for transcription and translation, but also for regulating cell proliferation, apoptosis, metastasis, and immunity. Aberrant expression of tDRs is associated with a wide range of human diseases, especially with tumorigenesis and tumor progression. The tumor microenvironment (TME) is a complex ecosystem consisting of various cellular and cell-free components that are mutually compatible with the tumor. It has been shown that tDRs regulate the TME by regulating cancer stem cells, immunity, energy metabolism, epithelial mesenchymal transition, and extracellular matrix remodeling, playing a pro-tumor or tumor suppressor role. In this review, the biogenesis, classification, and function of tDRs, as well as their effects on the TME and the clinical application prospects will be summarized and discussed based on up to date available knowledge.
Recent advances of small extracellular vesicle biomarkers in breast cancer diagnosis and prognosis
Authors: Yujin Lee, Jie Ni, Julia Beretov, Valerie C. Wasinger, Peter Graham, Yong Li
Journal: Molecular Cancer (2023)

Abstract Current clinical tools for breast cancer (BC) diagnosis are insufficient but liquid biopsy of different bodily fluids has recently emerged as a minimally invasive strategy that provides a real-time snapshot of tumour biomarkers for early diagnosis, active surveillance of progression, and post-treatment recurrence. Extracellular vesicles (EVs) are nano-sized membranous structures 50–1000 nm in diameter that are released by cells into biological fluids. EVs contain proteins, nucleic acids, and lipids which play pivotal roles in tumourigenesis and metastasis through cell-to-cell communication. Proteins and miRNAs from small EVs (sEV), which range in size from 50–150 nm, are being investigated as a potential source for novel BC biomarkers using mass spectrometry-based proteomics and next-generation sequencing. This review covers recent developments in sEV isolation and single sEV analysis technologies and summarises the sEV protein and miRNA biomarkers identified for BC diagnosis, prognosis, and chemoresistance. The limitations of current sEV biomarker research are discussed along with future perspective applications.
DNA methylation entropy as a measure of stem cell replication and aging
Authors: Himani Vaidya, Hye Seon Jeong, Kelsey Keith, Shinji Maegawa, Gennaro Calendo, Jozef Madzo, Jaroslav Jelinek, Jean-Pierre J. Issa
Journal: Genome biology (2023)

Abstract Background Epigenetic marks are encoded by DNA methylation and accumulate errors as organisms age. This drift correlates with lifespan, but the biology of how this occurs is still unexplained. We analyze DNA methylation with age in mouse intestinal stem cells and compare them to nonstem cells. Results Age-related changes in DNA methylation are identical in stem and nonstem cells, affect most prominently CpG islands and correlate weakly with gene expression. Age-related DNA methylation entropy, measured by the Jensen-Shannon Distribution, affects up to 25% of the detectable CpG sites and is a better measure of aging than individual CpG methylation. We analyze this entropy as a function of age in seven other tissues (heart, kidney, skeletal muscle, lung, liver, spleen, and blood) and it correlates strikingly with tissue-specific stem cell division rates. Thus, DNA methylation drift and increased entropy with age are primarily caused by and are sensors for, stem cell replication in adult tissues. Conclusions These data have implications for the mechanisms of tissue-specific functional declines with aging and for the development of DNA-methylation-based biological clocks.
An overview of DNA methylation-derived trait score methods and applications
Authors: Marta F. Nabais, Danni A. Gadd, Eilis Hannon, Jonathan Mill, Allan F. McRae, Naomi R. Wray
Journal: Genome biology (2023)

Abstract Microarray technology has been used to measure genome-wide DNA methylation in thousands of individuals. These studies typically test the associations between individual DNA methylation sites (“probes”) and complex traits or diseases. The results can be used to generate methylation profile scores (MPS) to predict outcomes in independent data sets. Although there are many parallels between MPS and polygenic (risk) scores (PGS), there are key differences. Here, we review motivations, methods, and applications of DNA methylation-based trait prediction, with a focus on common diseases. We contrast MPS with PGS, highlighting where assumptions made in genetic modeling may not hold in epigenetic data.
Broadly neutralizing anti-S2 antibodies protect against all three human betacoronaviruses that cause deadly disease
Authors: Panpan Zhou, Ge Song, Hejun Liu, Meng Yuan, Wan-ting He, Nathan Beutler, Xueyong Zhu, Longping V. Tse, David R. Martinez, Alexandra Schäfer, Fabio Anzanello, Peter Yong, Linghang Peng, Katharina Dueker, Rami Musharrafieh, Sean Callaghan, Tazio Capozzola, Oliver Limbo, Mara Parren, Elijah Garcia, Stephen A. Rawlings, Davey M. Smith, David Nemazee, Joseph G. Jardine, Yana Safonova, Bryan Briney, Thomas F. Rogers, Ian A. Wilson, Ralph S. Baric, Lisa E. Gralinski, Dennis R. Burton, Raiees Andrabi
Journal: Immunity (2023)

Pan-betacoronavirus neutralizing antibodies may hold the key to developing broadly protective vaccines against novel pandemic coronaviruses and to more effectively respond to SARS-CoV-2 variants. The emergence of Omicron and subvariants of SARS-CoV-2 illustrates the limitations of solely targeting the receptor-binding domain (RBD) of the spike (S) protein. Here, we isolated a large panel of broadly neutralizing antibodies (bnAbs) from SARS-CoV-2 recovered-vaccinated donors, which targets a conserved S2 region in the betacoronavirus spike fusion machinery. Select bnAbs showed broad in vivo protection against all three deadly betacoronaviruses, SARS-CoV-1, SARS-CoV-2, and MERS-CoV, which have spilled over into humans in the past two decades. Structural studies of these bnAbs delineated the molecular basis for their broad reactivity and revealed common antibody features targetable by broad vaccination strategies. These bnAbs provide new insights and opportunities for antibody-based interventions and for developing pan-betacoronavirus vaccines.
Genetics of sexually dimorphic adipose distribution in humans
Authors: Grace T. Hansen, Débora R. Sobreira, Zachary T. Weber, Alexis G. Thornburg, Ivy Aneas, Li Zhang, Noboru J. Sakabe, Amelia C. Joslin, Gabriela A. Haddad, Sophie M. Strobel, Samantha Laber, Farhath Sultana, Faezeh Sahebdel, Kohinoor Khan, Yang I. Li, Melina Claussnitzer, Liang Ye, Ricardo A. Battaglino, Marcelo A. Nóbrega
Journal: Nature Genetics (2023)
Genome editing coming of age for hemoglobinopathy
Authors: Haiyan Jiang
Journal: Molecular Therapy (2023)

Following remarkable developments in the past 10 years, CRISPR-Cas9-based genome editing is coming of age and poised to offer a functional cure for severe β-hemoglobinopathy, including transfusion-dependent thalassemia and sickle cell disease (SCD).
Matching mechanical heterogeneity of the native spinal cord augments axon infiltration in 3D-printed scaffolds
Authors: Kiet A. Tran, Brandon J. DeOre, David Ikejiani, Kristen Means, Louis S. Paone, Laura De Marchi, Łukasz Suprewicz, Katarina Koziol, Julien Bouyer, Fitzroy J. Byfield, Ying Jin, Penelope Georges, Itzhak Fischer, Paul A. Janmey, Peter A. Galie
Journal: Biomaterials (2023)
Re: Outpatient Photodynamic Diagnosis–guided Laser Destruction of Bladder Tumors Is as Good as Conventional Inpatient Photodynamic Diagnosis–guided Transurethral Tumor Resection in Patients with Recurrent Intermediate-risk Low-grade Ta Bladder Tumors. A Prospective Randomized Noninferiority Clinical Trial
Authors: Marco Moschini, Francesco Montorsi
Journal: European Urology (2023)
Liquid biopsies, are we ready for prime time?
Authors: Nicola Normanno, Kathi Apostolidis, Mark Stewart
Journal: Journal for ImmunoTherapy of Cancer (2023)

The possibility to use a simple peripheral blood sample to make an early diagnosis of cancer, to gain information on the genomic profile of the tumor, and to predict prognosis and the probability to respond to therapy has fascinated researchers and clinicians for many years. The improvement of
Regulatory implications of ctDNA in immuno-oncology for solid tumors
Authors: Paz J Vellanki, Soma Ghosh, Anand Pathak, Michael J Fusco, Erik W Bloomquist, Shenghui Tang, Harpreet Singh, Reena Philip, Richard Pazdur, Julia A Beaver
Journal: Journal for ImmunoTherapy of Cancer (2023)

In the era of precision oncology, use of circulating tumor DNA (ctDNA) is emerging as a minimally invasive approach for the diagnosis and management of patients with cancer and as an enrichment tool in clinical trials. In recent years, the US Food and Drug Administration has approved multiple ctDNA-based companion diagnostic assays for the safe and effective use of targeted therapies and ctDNA-based assays are also being developed for use with immuno-oncology-based therapies. For early-stage solid tumor cancers, ctDNA may be particularly important to detect molecular residual disease (MRD) to support early implementation of adjuvant or escalated therapy to prevent development of metastatic disease. Clinical trials are also increasingly using ctDNA MRD for patient selection and stratification, with an ultimate goal of improving trial efficiency through use of an enriched patient population. Standardization and harmonization of ctDNA assays and methodologies, along with further clinical validation of ctDNA as a prognostic and predictive biomarker, are necessary before ctDNA may be considered as an efficacy-response biomarker to support regulatory decision making.